Method of inducing the differentiation of stem cells into myocardial cells

Abstract

For a method of inducing differentiation of cardiomyocytes from stem cells, a method is provided to induce efficiently and selectively differentiation of cardiomyocytes by such a method in which the stem cells are cultured to induce differentiation into cardiomyocytes in the presence of a substance that inhibits BMP signaling.

1. A method for inducing differentiation of cardiomyocytes from mammalian pluripotent stem cells, comprising
 (1) culturing mammalian pluripotent stem cells in a culture medium including a substance that inhibits BMP signaling within three days before inducing differentiation and/or within the first three days of the differentiation-inducing stage; and 
 (2) obtaining cardiomyocytes. 
 
     
     
       2. The method according to  claim 1 , wherein the step of culturing stem cells comprises a step of forming embryoid bodies by floating aggregation culture. 
     
     
       3. The method according to  claim 1 , wherein the step of culturing stem cells comprises a step of co-culturing with feeder cells. 
     
     
       4. The method according to  claim 1 , wherein the step of culturing stem cells comprises a step of plate culturing on a culture container. 
     
     
       5. The method according to  claim 1 , wherein said culturing occurs within the first three days of the differentiation-inducing stage. 
     
     
       6. The method according to  claim 1 , wherein said culturing occurs within three days before inducing differentiation. 
     
     
       7. The method according to  claim 1 , wherein said culturing occurs within three days before inducing differentiation, and within the first three days of the differentiation-inducing stage. 
     
     
       8. The method according to  claim 1 , wherein the substance that inhibits BMP signaling is a BMP antagonist. 
     
     
       9. The method according to  claim 8 , wherein the BMP antagonist is one or more selected from a group comprising Noggin, Chordin, fetuin, follistatin, sclerostin, DAN, Cerberus, gremlin, Dante and related proteins thereof. 
     
     
       10. The method according to  claim 1 , wherein the pluripotent stem cells are embryonic stem cells, cells with a similar morphology to embryonic stem cells, embryonic germ cells, or multipotent adult progenitor cells. 
     
     
       11. The method according to  claim 1 , wherein the pluripotent stem cells are embryonic stem cells. 
     
     
       12. The method according to  claim 1 , wherein said culturing occurs within three days before inducing differentiation, and at the beginning of the differentiation-inducing stage. 
     
     
       13. A method for inducing differentiation of cardiomyocytes from mammalian pluripotent stem cells, comprising
 (1) culturing mammalian pluripotent stem cells in a culture medium including a substance that inhibits BMP signaling within three days before the formation of embryoid bodies and/or within the first three days after the formation of embryoid bodies; and 
 (2) obtaining cardiomyocytes. 
 
     
     
       14. The method according to  claim 13 , wherein said culturing occurs within three days before the formation of embryoid bodies. 
     
     
       15. The method according to  claim 13 , wherein said culturing occurs within the first three days after the formation of embryoid bodies. 
     
     
       16. The method according to  claim 13 , wherein said culturing occurs within three days before the formation of embryoid bodies and within the first three days after the formation of embryoid bodies. 
     
     
       17. The method according to  claim 16 , wherein said culturing occurs within three days before the formation of embryoid bodies and immediately after the formation of embryoid bodies.